Specific binding

The phosphorodithioates DNA derivatives have been shown to bind specifically to complementary DNA or ENA sequences to form stable adducts. Because they are also highly resistant to degradation by cellular exonucleases, these derivatives can be useful both for appHcations in research and as therapeutic dmgs. Phosphorodithioate DNA has been shown to stimulate Rnase H activity in nuclear cell extracts and is a potent inhibitor of HIV type-1 reverse transcriptase (56). [Pg.262]

Cellular protein biosynthesis involves the following steps. One strand of double-stranded DNA serves as a template strand for the synthesis of a complementary single-stranded messenger ribonucleic acid (mRNA) in a process called transcription. This mRNA in turn serves as a template to direct the synthesis of the protein in a process called translation. The codons of the mRNA are read sequentially by transfer RNA (tRNA) molecules, which bind specifically to the mRNA via triplets of nucleotides that are complementary to the particular codon, called an anticodon. Protein synthesis occurs on a ribosome, a complex consisting of more than 50 different proteins and several stmctural RNA molecules, which moves along the mRNA and mediates the binding of the tRNA molecules and the formation of the nascent peptide chain. The tRNA molecule carries an activated form of the specific amino acid to the ribosome where it is added to the end of the growing peptide chain. There is at least one tRNA for each amino acid. [Pg.197]

The elegant genetic studies by the group of Charles Yanofsky at Stanford University, conducted before the crystal structure was known, confirm this mechanism. The side chain of Ala 77, which is in the loop region of the helix-turn-helix motif, faces the cavity where tryptophan binds. When this side chain is replaced by the bulkier side chain of Val, the mutant repressor does not require tryptophan to be able to bind specifically to the operator DNA. The presence of a bulkier valine side chain at position 77 maintains the heads in an active conformation even in the absence of bound tryptophan. The crystal structure of this mutant repressor, in the absence of tryptophan, is basically the same as that of the wild-type repressor with tryptophan. This is an excellent example of how ligand-induced conformational changes can be mimicked by amino acid substitutions in the protein. [Pg.143]

The homeodomain frequently binds to DNA as a monomer, in contrast to procaryotic DNA-binding proteins containing tbe belix-turn-helix motif, which usually bind as dimers. In vitro tbe homeodomain binds specifically to... [Pg.160]

How is the binding specificity of the heterodimer achieved compared with the specificity of Mat a2 alone The crystal structure rules out the simple model that the contacts made between the Mat a2 homeodomain and DNA are altered as a result of heterodimerization. The contacts between the Mat o2 homeodomain and DNA in the heterodimer complex are virtually indistinguishable from those seen in the structure of the Mat o2 monomer bound to DNA. However, there are at least two significant factors that may account for the increased specificity of the heterodimer. First, the Mat al homeodomain makes significant contacts with the DNA, and the heterodimeric complex will therefore bind more tightly to sites that provide the contacts required by both partners. Second, site-directed mutagenesis experiments have shown that the protein-protein interactions involving the... [Pg.163]

The ability of the leucine zipper proteins to form heterodimers greatly expands the repertoire of DNA-binding specificities that these proteins can display. As illustrated in Figure 10.19, for example, three distinct DNA-binding specificities could, in principle, be generated from two types of monomer, while six could be created from three types of monomer and so on. This is an example of combinatorial control, in which combinations of proteins, rather than individual proteins, control a cellular process. It is one of the most important mechanisms used by eucaryotic cells to control gene expression. [Pg.193]

Figure 10.19 Heterodimerization of leucine zipper proteins can alter their DNA-binding specificity. Leucine zipper homodimers bind to symmetric DNA sequences, as shown In the left-hand and center drawings. These two proteins recognize different DNA sequences, as indicated by the red and blue regions in the DNA. The two different monomers can combine to form a heterodimer that recognizes a hybrid DNA sequence, composed of one red and one blue region.

Signal-transducing receptors are plasma membrane proteins that bind specific molecules, such as growth factors, hormones, or neurotransmitters, and then transmit a signal to the cell s interior, causing the cell to respond in a... [Pg.278]

How do the mutations identified by phage display improve binding specificity There is as yet no direct stmctural information on the phage-selected inhibitors however they can be modeled using data from the crystal structures of other Kunitz domains bound to serine proteinases. These studies lead to the conclusion that the mutations identified by phage display improve binding specificity by maximizing complementarity between the... [Pg.362]

A protein interacts with a metabolite. The metabolite is dins a ligand which binds. specifically to this protein... [Pg.157]

Ultrafiltration of micellar solutions combines the high permeate flows commonly found in ultrafiltration systems with the possibility of removing molecules independent of their size, since micelles can specifically solubilize or bind low molecular weight components. Characteristics of this separation technique, known as micellar-enhanced ultrafiltration (MEUF), are that micelles bind specific compounds and subsequent ultrafiltration separates the surrounding aqueous phase from the micelles [70]. The pore size of the UF membrane must be chosen such, that the micelles are retained but the unbound components can pass the membrane freely. Alternatively, proteins such as BSA have been used in stead of micelles to obtain similar enan-tioselective aggregates [71]. [Pg.145]

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